Project Summary When we fall asleep, the world around us doesn't stop producing stimuli. Preparing for sleep, most animals seek out a secluded spot that not only protects them from predators, but also helps filter out some of the sensory information that is constantly bombarding our senses. In addition to this behavioral filtering, the brain itself filters information during sleep. We propose that by studying how sensory information is gated during sleep, we can gain insight into how sensory awareness is generated in the brain. We are establishing novel experimental platforms that exploit the dynamic arousal threshold during sleep in Drosophila melanogaster, a powerful model for the genetic dissection of nervous system function. We will look for genes and neurons that gate sensory information during sleep. Sleep in Drosophila displays many characteristics of mammalian sleep, and known sleep factors are conserved between flies and us. We will use the fly to understand another puzzle that interests us - how animals regulate their sleep amount. We are all familiar with the drowsy feeling that results from inadequate sleep, when all we want to do is crawl back to bed. The need for sleep can be overwhelming, and this is due to the essential nature of this behavior. But what is this feeling, where does it come from? Despite longstanding interest in this question, we do not have any mechanistic insights into how sleep homeostasis ? the physiological balance between waking and sleep - is regulated. Using the same system we designed to probe arousal threshold, we can deprive flies of sleep in a high-throughput and automated manner, and look for animals whose rebound sleep deviates from normal. Our approach is particularly innovative in using the same system to study two distinct but essential biological questions. Finding animals that do not sense the loss of sleep, or cannot respond adequately, will afford an opportunity to study molecular and neural correlates of sleep homeostasis. This is of great relevance for human health, as sleep disturbances underlie many significant health problems including depression, diabetes and cancer.